F2-isoprostanes are a specific marker of lipid peroxidation and measurement of these molecules can provide a sensitive reliable marker of oxidative damage in vivo. We found that smokers have significantly increased levels of F2-isoprostanes both free in the circulation and esterified to plasma lipids. Following cessation of smoking for 2 weeks, levels fell significantly. These results provide the first convincing evidence that smoking causes oxidative damage in vivo in humans.